1. Field of the Invention
The present invention relates generally to fluid delivery devices. More particularly, the invention concerns an improved apparatus for infusing medicinal agents into an ambulatory patient at specific rates over extended periods of time, which apparatus includes fluid flow indicator means and a novel adjustable flow rate control means for precisely adjustably controlling the rate of fluid flow from the reservoir of the device.
2. Discussion of the Prior Art
The biotechnology industry emerged in the 1980s as new molecular biological techniques made possible the commercial production of proteins, peptides and other biopharmaceuticals. These molecules are integral to numerous physiological processes and have enormous therapeutic potential as oncolytics, hormones, analgesics, antihypertensives, growth factors and others. It is believed that at the present time there are currently over 600 biotech drugs in advanced stages of development.
Because bioengineered molecules often have an extremely short biological half-life and poor bioavailability, continuous infusion is often considered to be a more economically and therapeutically practical route of drug delivery than oral, ocular, nasal, buccal, intestinal, rectal or pulmonary administration. As will be better appreciated from the discussion that follows, the apparatus of the present invention has been specifically engineered for these emerging therapies and will allow highly safe and accurate microscaled ambulatory infusion of drugs with narrow therapeutic windows. In one form of the invention, the apparatus will accept either 1.5 or 3.0 mL vial cartridges of injectable agent, consistent with the expected dosing requirements of many biopharmaceuticals now under development.
Many of the pharmacologic agents now under development possess a very narrow range of therapeutic effectiveness, for instance, too small a dose results in no effect, while too great a dose results in toxic reaction. Additionally, the ever increasing medicinal use of proteins and peptides has created many challenging new problems concerning means for the effective delivery of the molecules to the patient. In general these molecules are difficult to stabilize and often undergo a variety of physical and chemical transformations including precipitation, aggregation and oxidation. Further, they are poorly absorbed after oral administration. Most proteins now being used or under development are given parenterally in order to insure rapid onset of action, with the main routes of delivery being intravenous, intramuscular, or subcutaneous. Intravenous administration results in the fastest, intramuscular injection is next, and subcutaneous injection exhibits the slowest onset of action. While other noninvasive methods of delivery, such as iontophoresis and nasal or buccal administration have been investigated, they have not been widely adopted.
A major advantage of infusion therapy is the opportunity to avoid repeated injections and to achieve a constant or controlled rate of delivery of the medicinal agents. Accordingly, many types of sophisticated electronic infusion devices have been suggested to achieve complex patterns of dosing which are customized to the patient""s need and do not require repeated injections in order to maintain a constant level of proteins in the blood. Another major advantage of infusion therapy over repeated needle injections resides in the fact that such therapy is less time consuming and considerably less costly because the caregiver can administer a single dose instead of multiple injections given over a period of time.
The primary disadvantage of infusion therapy is its limiting effect on the patient""s lifestyle. This is largely due to the physical size of the prior art devices and the many precautions associated with parenteral therapy. Additionally, many of the prior art portable electromechanical devices are generally quite fragile and must be carefully handled to avoid breakage and preclude operational malfunction. Experience has shown that while a patient will tolerate restrictions on an active lifestyle for short periods of time, long-term use of the prior art devices have tended to create significant patient intolerance. In addition to the precautions associated with using the prior art devices, there are numerous logistical issues of battery changing and frequent replacement and the dedicated pump accessories. These logistical issues substantially contribute to the overall cost and complexity of prior art infusion therapy.
The unique combination of features in the apparatus of the present invention make it superior to virtually all currently existing competitive systems. For example, although stationary electronic syringe pumps offer an excellent flow rate accuracy of 3-10%, they are expensive, high maintenance devices and do not allow patient mobility. Recently, portable, miniaturized versions of these syringe pumps have been developed which allow greater freedom; however, they are often fragile, non-waterproof and complicated to use, requiring battery and accessory changes. Also problematic is the fact that both of the latter two types of devices often require drugs to be diluted for parenteral administration, which may lead to unnecessary patient overhydration. In addition to syringe systems, depot delivery (via subcutaneous or intramuscular implants) has been developed for continuous infusion; however, its high cost, invasiveness and inability to provide drug stability makes it an unattractive alternative to potential users.
Because the present application discloses improvements to the apparatus described in the U.S. Ser. No. 08/768,663, this co-pending application is also hereby incorporated by reference in its entirely as though fully set forth herein.
The elastomeric film materials used in the apparatus of the present invention, as well as various alternate constructions are described in detail in U.S. Pat. No. 5,205,820 issued to one of the present inventors. Therefore, U.S. Pat. No. 5,205,820 is also incorporated by reference in its entirety as though fully set forth herein.
As will be better appreciated from the discussion that follows, the apparatus of the invention can be used with minimal professional assistance in an alternate health care environment, such as the home. By way of example, the completely mechanical devices of the invention can be comfortably and conveniently removably affixed to the patient""s body and can be used for continuous infusion of various medicinal agents over substantial periods of time.
Because the present invention comprises an improvement over the embodiments of the invention described in Ser. No. 08/768,663, this latter application is incorporated herein by reference as though fully set for the herein. While the inventions described in Ser. No. 08/768,663 comprise fluid delivery devices having a fluid reservoir and an indicator assembly for indicating fluid flow through the apparatus they do not include the highly novel, adjustable fluid flow rate mechanism of the present invention which enables the fluid contained within the reservoir of the device to be precisely dispensed at various selected rates. As will be better understood from the description which follows, the novel adjustable fluid flow rate control mechanism of the present invention also includes novel locking means for preventing unauthorized adjustment of the rate control mechanism. This novel locking means is operable only by a physician or health care worker who is in possession of a physician operating key. Accordingly, once a particular flow rate is selected, the patient cannot unilaterally change the flow rate.
It is an object of the present invention to provide an apparatus for expelling fluids at a precisely controlled rate that is of a compact laminate construction. More particularly, it is an object of the invention to provide such an apparatus that can be used for the precise infusion of pharmaceutical agents, including proteins and peptides into an ambulatory patient at controlled rates over extended periods of time.
It is an object of the present invention to provide an apparatus of the aforementioned character which is highly reliable and easy-to-use by lay persons in a non-hospital environment.
Another object of the invention is to provide an apparatus which can be factory prefilled with a wide variety of medicaments or one which can readily be filled in the field shortly prior to use.
A further object of the invention is to provide a low profile, fluid delivery device of laminate construction which can be manufactured inexpensively in large volume by automated machinery.
Another object of the invention is to provide a device of the aforementioned character which includes novel fluid flow control means that are disposed intermediate the fluid reservoir outlet and the outlet port of the device for precisely controlling the flow of fluid flow from the outlet port toward the patient.
Another object of the invention is to provide an apparatus of the aforementioned character in which the fluid flow control means comprises rate control means that includes a rotatable flow restrictor support disk that can be rotated by the treating physician to selectively position the flow restrictor between the fluid reservoir and the device outlet port so as to precisely control the rate of flow of beneficial agents from the fluid reservoir toward the patient.
Another object of the present invention is to provide a flow rate control means of the type described in the preceding paragraph in which the flow restrictors comprise porous frits of varying porosity.
Another object of the present invention is to provide a flow rate control means in which the flow restrictors comprise a laser drilled thin film.
Another object of the invention is to provide an apparatus as described in the preceding paragraphs which includes locking means for locking the variable flow rate control means in a preset position so that the rate control can be set only by the treating physician or an authorized health care worker having an operating key.
Another object of the invention is to provide an apparatus of the aforementioned character in which the stored energy source is of a novel construction that can be precisely tailored to continuously deliver fluid from the device to the patient Another object of the invention is to provide fill means for use in controllably filling the fluid reservoir of the apparatus.
Another object of the invention is to provide a novel vial assembly for use with the fluid dispenser subassembly of the apparatus which is easy to use, is inexpensive to manufacture, and one which maintains the vial in an aseptic condition until time of use.
Other objects of the invention are set forth in U.S. Pat. No. 5,205,820 which is incorporated herein and still further objects will become more apparent from the discussion which follows.
By way of summary, the fluid delivery apparatus of the present form of the invention comprises two cooperating components, namely a fluid dispenser and a novel, adjustable fluid flow control assembly for selecting the desired fluid flow rate to the patient. The fluid dispenser, which readily lends itself to automated manufacture, is generally similar to that described in copending Ser. No. 09/165,713, which application is incorporated herein by reference and includes a base and a stored energy means comprising at least one distendable elastomeric membrane which cooperates with the base to form a fluid reservoir. In at least one form of the invention, the fluid dispenser includes a novel infusion means that can be conveniently stored in a forward compartment of the device housing.